Plasma Levels of Galectin-9 Reflect Disease Severity in Malaria Infection
Overview
Authors
Affiliations
Background: Galectin-9 (Gal-9) is a β-galactoside-binding lectin that interacts with sugar moieties on glycoproteins and glycolipids of cells and pathogens. Gal-9 is known as an immune modulator that induces cell death via interaction with T cell immunoglobulin and mucin domain-3 (Tim3), a co-inhibitory receptor, and it inhibits production of several pro-inflammatory cytokines (TNF, IL-6 and IL-1α) and enhances production of IL-10. To understand the immune pathology of malaria, the Gal-9 in plasma was measured.
Methods: Plasma samples and clinical parameters were obtained from 50 acute malaria cases (nine severe and 41 uncomplicated cases) from Thailand at three time points: day 0, day 7 and day 28. Gal-9 levels were determined by ELISA. A total of 38 species of cytokines and chemokines were measured using a BioPlex assay.
Results: Gal-9 levels were higher at day 0 compared to day 7 and day 28 (P < 0.0001). Gal-9 levels were also higher in severe malaria (SM) cases compared to uncomplicated (UM) cases at day 0 and day 7 (923 vs 617 pg/mL; P = 0.03, and 659 vs 348 pg/mL; P = 0.02 respectively). Median Gal-9 levels were higher in patients with blood urea nitrogen to creatinine ratio (BUN/creatinine) ≥20 (mg/dL) than in patients with BUN/creatinine <20 (mg/dL) at day 0 (817.3 vs 576.2 pg/mL, P = 0.007). Gal-9 was inversely significantly correlated with chloride levels in both SM and UM cases (r s = -0.73 and r s = -0.46, respectively). In both UM and SM cases, Gal-9 was significantly associated with pro- and anti-inflammatory cytokines and chemokines such as TNF, IL-6, IFN-α2, IFN-γ, IL-1Ra and IL-10. These correlations were observed at day 0 but disappeared at day 28.
Conclusions: Gal-9 is released during acute malaria, and reflects its severity. This elevation of Gal-9 in acute malaria infection raises the possibility of its role in termination of the immune response by binding to Tim-3, a receptor of Gal-9.
Tull S, Saviano A, Fatima A, Begum J, Mansour A, Marigliano N Biomed Pharmacother. 2025; 184:117902.
PMID: 39951917 PMC: 11870847. DOI: 10.1016/j.biopha.2025.117902.
Galectins in Protozoan Parasitic Diseases: Potential Applications in Diagnostics and Therapeutics.
Meira C, Silva J, Quadros H, Silva L, Barreto B, Rocha V Cells. 2023; 12(23).
PMID: 38067100 PMC: 10705098. DOI: 10.3390/cells12232671.
Relation between Increased IL-10 Levels and Malaria Severity: A Systematic Review and Meta-Analysis.
Sornsenee P, Wilairatana P, Kotepui K, Masangkay F, Romyasamit C, Kotepui M Trop Med Infect Dis. 2023; 8(1).
PMID: 36668942 PMC: 9865813. DOI: 10.3390/tropicalmed8010035.
The spectrum of clinical biomarkers in severe malaria and new avenues for exploration.
Foko L, Narang G, Tamang S, Hawadak J, Jakhan J, Sharma A Virulence. 2022; 13(1):634-653.
PMID: 36036460 PMC: 9427047. DOI: 10.1080/21505594.2022.2056966.
Li S, Zhu Y, Wang S, Li Y, Pang N, An M Mol Biol Rep. 2022; 49(8):7497-7506.
PMID: 35715604 DOI: 10.1007/s11033-022-07554-3.